The long term objectives of this plan are the investigation of specific aspects of tumor biology/radiobiology, namely reoxygenation, cell migration, cell recruitment, and the relationship between cell sensitivity and cell kinetics. The specific aims under reoxygenation include determining kinetics within the SCCVII tumor and comparing these for tumor specificity with our earlier RIF-1 studies, investigating reoxygenation after hyperfractionated irradiation, and examining the effect of cytotoxic drugs on reoxygenation. Tumor cell migration studies will investigate tumor cell migration in spheroids that are implanted intraperitoneally; determine whether irradiation effects cell migration within and away from spheroids that rest on collagen sheets; compare the migratory ability of cells grown on glass or plastic culture surfaces with the same cells on collagen sheets; and examine the migratory ability of normal and neoplastic cells, using 10T1/2 and 3T3 cells, contrasted with our EMT6 and RIF-1 data. Cell recruitment, sensitivity, and kinetic studies will characterize the radiosensitivity of P and Q cells in EMT6, RIF-I and SCCVII tumors; investigate whether recruitment of Q cells into P cells is affected by irradiation and by cytotoxic drugs; determine microcolony abortion probabilities; determine whether the mode of X-ray dose fractionation affects growth kinetics of surviving clonogenic tumor cells; and provide data on the kinetics of cell death and the division delay dependence caused by chemotherapeutic drugs. All animal studies will be done with inbred SPF mice. Tumor response will be assayed either by regrowth delay or colony growth. This health-related project is directly applicable to human cancer therapy.